Abstract

The growing production and use of engineered nanomaterials (ENMs) has raised considerable concern regarding their implicated environmental and health risks. Therefore, there is an urgent need to understand the toxic effects and mechanisms of these ENMs. Our group has applied toxicogenimic approach for mechanistic assessment ENMs. The results revealed that although the stress response and the potential toxic mechanisms varied among the ENMs tested, the oxidative stress, DNA damage, and protein stress are the most important toxicity mechanisms for all the ENMs examined. Most ENMs caused oxidative stress as well as cell membrane and transportation damage. We revealed detailed information of the involvement of different DNA damage and repair genes, suggesting that some NMs cause DNA damage via recognized SOS pathway, while others do not.
To link the toxicogenomic results with regulatory benchmarks and conventional toxicity assessment endpoints, we determined the Non Observed Transcriptional Level (NOTEL) for all the ENMs based on the dose-response curves obtained. The NOTEL values correlated with the endpoints proposed by others for nanotoxicity assessment. We also proposed a new ToxicoGenomic Response Indicator (TGRI) and the TGRI correlated well with those established endpoints (e.g. NOTEL, Biological Oxidative Damage), indicating that it can be potentially employed as a regulatory benchmark and toxicity assessment endpoint. Our results demonstrated that the proposed prokaryotic toxicogenomic approach using whole-cell arrays promises to be a feasible method for quantitative toxicity assessment of ENMs.